Genetic and Environmental Factors

Evidence of a genetic component in the etiology of NTDs includes familial recurrence patterns, ethnic variation, and sex variation (more common in females). More direct evidence of the role of genetic factors is the discovery that the gene encoding for the thermolabile variant of the 5,10-methylene-tetrahydrofolate reductase enzyme is more common in individuals with spina bifida than in controls. The most striking environmental, or nongenetic, factors are the protective effect of folic acid and the marked variations in prevalence over time and between areas. The prevalence rates of NTDs at birth have been falling in most countries, particularly in regions that traditionally had high rates. It is assumed, but not scientifically proven, that better nutrition is a main factor determining this trend. Variations with season, social class (more common in disadvantaged groups), and, to a lesser extent, maternal age and reproductive history provide further evidence of the role of environmental factors. Several of these factors may be explained in whole or in part on nutritional grounds.

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